The long-term objective of the proposed study is to examine the role of the chemokine CXCL12, an immune system molecule, in cognitive functioning. Cognition is the active intellectual processes through which information is obtained, transformed, stored, and used to help define us as individuals. Survival depends upon the healthy cognitive functioning of learning and memory, allowing adaptation to individual experiences and promoting well-being. Understanding the mechanisms that regulate learning and memory will help optimize the development of strategies to offset cognitive decline or loss. Increasing evidence shows that immune system molecules involved in injury and the inflammatory response, such as cytokines, play a role in the physiologic development and modulation of the central nervous system. Current reports show that cytokines play a role in cognitive functioning and because chemokines are similar to cytokines, it is reasonable to suggest that they may also have an effect on cognition. Our preliminary data show that the specific chemokine, CXCL12, plays a role in learning and memory under normal physiological conditions. However, the underlying mechanism on how CXCL12 and its corresponding receptor, CXCR4, affect the complex central nervous system function of cognition is not well understood. A likely but poorly understood physiologic mechanism regulating learning and memory is adult neurogenesis, a life-long process of generating new neurons which must successfully integrate into an existing neuronal network and may represent new memories. The intricate process of regulating adult neurogenesis involves many molecular mechanisms. We hypothesize that effects of CXCL12/CXCR4 signaling on cognitive functioning may be mediated by endogenous adult neurogenesis in the hippocampus (brain region involved in learning and memory) given that neurogenesis has been shown to play an important role in learning and memory. Thus, the specific aim of the study is to examine the effects of CXCL12/CXCR4 signaling on neurogenesis and its relationship to learning and memory. PUBLIC HEALTH RELEVANCE: Survival depends upon the healthy cognitive functioning of learning and memory, allowing adaptation to individual experiences and promoting well-being. Understanding the cellular and molecular mechanisms that regulate learning and memory will help optimize the development of strategies to offset cognitive decline or loss.